Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnosis of essential thrombocythemia in a cat was made by fulfilling the five applicable criteria set forth by the Polycythemia Vera Study Group for use in humans. The criteria were 1) a platelet count persistently above 600,000/microL, 2) a normal initial hematocrit that did not rise in response to iron therapy, 3) normal serum iron concentration, 4) absence of collagen fibrosis of the bone marrow, and 5) no cause for reactive thrombocytosis. In addition, normal thrombopoietin concentrations and splenic hypofunction were demonstrated. Melphalan was not effective in decreasing the platelet count and the cat died of sepsis.
 ...
PMID:Essential thrombocythemia in a cat. 234 25

The armistice after World War II marked the beginning of an era that was to last to the end of the present century. It was an era in which many changes in medicine and nursing combined to alter the entire philosophy of managing malignant disease. More specifically, the fluid-phase tumors, which comprise myelodysplasia and the leukemias, were singled out for special attention. First there was the ease with which blood and bone marrow could be sampled, making serial investigations simple and practical. Second, cytotoxic drugs became available ranging from nitrogen mustard through cytosine arabinoside, the anthracycline antibiotics, and the epi-podophyllotoxins. Although cytomorphology of the hematopoietic tissue had been exquisitely defined with the use of Romanowsky stains coupled with electron microscopy, the diagnosis of leukemia was, before 1945, a death sentence for want of effective therapy. This changed dramatically with the introduction of the folate antagonists, and progress was unremitting as the range of new products expanded. Suddenly responses could be obtained with single agents, and fairly rapidly combinations were developed for cumulative antitumor effect. Many agents had undesirable toxicity among different organs. Although slightly different for myeloblastic or lymphoblastic variants, this approach produced apparent disease eradication. The concept of complete remission, both clinical and hematologic, was born. Some of our early enthusiasm has had to be tempered with the somber appreciation that not all patients can improve and many others experience relapses. Where then do we stand? Leukemic cells themselves seldom kill. It is the relentless and uncontrolled expansion of a neoplastic clone that leads to bone marrow failure, albeit at different rates in the various subtypes. In the acute forms, the common presentation remains symptomatic anemia, neutropenic sepsis, and thrombocytopenic bleeding. Differentiation from marrow aplasia may not be possible at first on clinical grounds, although bone tenderness, gingival hypertrophy, and skin infiltration are among the general useful differential signs. Findings in the circulation and the marrow are of cardinal importance in diagnosis; they provide the basis for classification. Improved accuracy has followed the introduction of cytochemical stains, and a widening range of monoclonal antibodies, and greater recourse to karyotyping, have enhanced diagnostic acumen. Treatment decisions rest on many variables or prognostic factors that include age, performance status, comorbidity, and disease category, with an ever increasing regard for the part played by cellular and molecular genetics. Despite skillful utilization of this wealth of information for optimal management, outcome often leaves much to be desired. Myelodysplasia encompasses a number of different syndromes in which the refractory anemias are indolent, whereas those with excess blasts progress toward overt leukemia. Considerable judgment is necessary in selecting patients for whom supportive therapy alone is appropriate and recognizing others, up to one third of patients for whom use growth factors that include erythropoietin, granulocyte or granulocyte monocyte-colony stimulating factors, and thrombopoietin can be justified. The often unfavorable result has been a stimulus to current investigations that examine the value of intensive chemotherapy or the more innovative bone marrow transplantation and its peripheral blood equivalent. Autografting is a newer alternative that does not have proved potential. Acute leukemia, whether myeloblastic or lymphoblastic, has been managed with mixed success. Remission rates have steadily increased and, notably among children, moved toward 100% in certain groupings. The downside of nonspecific drug regimens is that some patients simply may not respond, whereas others experience remissions and then relapses. (ABSTRACT TRUNCATED)
 ...
PMID:Myelodysplasia and the leukemias. 930 44

Thrombocytopenia is a commonly encountered hematologic complication in neonates with sepsis. Thrombopoietin (TPO) is the principal physiologic regulator of megakariocytopoiesis and platelet production. This study was carried out to determine whether variations in circulating TPO levels would occur in infected neonates and/or if they would correlate with platelet counts. In a prospective study of 36 sick neonates (gestational age 24-42 wk) admitted to a regional Neonatal Intensive Care Unit (NICU), blood was collected for TPO measurements and platelet counts on admission to the NICU, if infection was inferred, and at recovery before discharge. An additional group of 15 apparently healthy neonates was also studied (median postnatal age at the time of blood sampling for TPO assessment: 4 d, range 1-10) as control. TPO was measured on plasma samples using a commercially available enzyme-immunosorbent assay (ELISA). On admission, the majority (21/36) of the sick neonates had non-infectious diseases, 2 had early onset sepsis, and 13 had infection (defined as the presence of clinical signs of sepsis, abnormal leukocyte counts or C-reactive protein values, and positive results on local cultures, but negative blood culture results). During the hospital stay, 5 neonates developed sepsis (positive blood culture) and 6 had infection (as previously defined) or necrotizing enterocolitis (NEC). The median TPO level (1704 pg/ml, range 51-3912) was higher during sepsis (either early or late) than during infection (included NEC) (198 pg/ml, range 21-2504), or non-infectious disease (659 pg/ml, range 0-2533), while platelet counts (median value 37,000 cells/microl, range 15,000-486,000) were lower than during either infection (included NEC) (median value 238,000 cells/microl, range 49,000-655,000) or non-infectious disease (median value 110,000 cells/microl, range 45,000-549,000). When infants had recovered from these illnesses, TPO concentrations markedly dropped (median value 59 pg/ml, range 0-825). These values were similar to those found in the control neonates (median TPO level 85 pg/ml, range 43-620). In infected neonates (sepsis plus infection), TPO levels inversely correlated with platelet counts (r = -0.634, p = 0.001) as did those of infants with non-infectious disease (r = -0.574, p = 0.006), while there was no significant correlation between TPO levels and platelet counts in the samples obtained after recovery or in the control infants. We conclude that infected neonates have high circulating TPO levels in the face of low platelet counts. Whether larger TPO concentrations following exogenous administration of recombinant TPO would restore the number of circulating platelets warrants further investigation.
 ...
PMID:Circulating thrombopoietin levels in neonates with infection. 1022 48

This review summarizes the biology of thrombopoietin (TPO) in childhood. Studies on TPO and its receptor (c-mpl) have improved the understanding of inherited and acquired thrombocytopenias in childhood. Data are presented in this review regarding the molecular biology of TPO, differences in cellular effects on megakaryopoiesis, the regulation of TPO production, and TPO concentrations in health and disease. For neonatal thrombocytopenia, the focus is on early-onset thrombocytopenia associated with maternal diabetes, pregnancy-induced hypertension, intrauterine growth retardation, hypoxia, and sepsis. Fetal alloimmune thrombocytopenia allows insight into the biology of TPO when fetal megakaryopoiesis is chronically stimulated. In the thrombocytopenia absent radii syndrome and congenital amegakaryocytic thrombocytopenia, thrombocytopenia is caused by a disorder in the signal transduction at the c-mpl level and respectively directly on c-mpl. TPO concentrations in other inherited thrombocytopenias such as Fanconi anemia, Shwachman syndrome, Wiskott-Aldrich syndrome, and Bernard-Soulier syndrome are discussed. For acquired thrombocytopenias, data on TPO in aplastic anemia, immune thrombocytopenia, human immunodeficiency virus infection, and liver disease are given. Possible indications for a treatment with recombinant TPO in childhood are discussed, but the criteria to identify patients who would benefit need detailed evaluation.
 ...
PMID:Thrombopoietin in thrombocytopenias of childhood. 1144 55

Thrombocytopenia is common in sick neonates, and affected neonates have adverse outcomes compared with those without thrombocytopenia. As impaired platelet production underlies many neonatal thrombocytopenias, affected neonates are potential candidates for hemopoietic growth factor therapy. Although recombinant human (rh) thrombopoietin remains under therapeutic development, rhIL-11, which stimulates megakaryocytopoiesis and increases platelet counts after chemotherapy, is already licensed for clinical use. However, nothing is known about IL-11 in neonates. We therefore measured plasma IL-11 by ELISA in healthy term neonates, stable preterm neonates with or without thrombocytopenia, and preterm neonates with sepsis or necrotizing enterocolitis (NEC) with or without thrombocytopenia. At birth IL-11 was undetectable (<10 pg/mL) in healthy term neonates (n = 20) and 27 of 31 (87%) stable preterm neonates. Three stable preterm neonates with detectable IL-11 (mean+/-SD, 11.3 +/- 0.4 pg/mL; median, 11.6 pg/mL) suffered chorioamnionitis, the remaining neonate (IL-11, 14 pg/mL) being one of nine with early onset thrombocytopenia (present by <72 h of age). IL-11 was also measured in 58 preterm neonates with suspected sepsis or NEC. In 25 of 58, sepsis or NEC was unconfirmed and IL-11 was undetectable. By contrast, 14 of 33 with proven sepsis or NEC had elevated IL-11 (median, 14.9 pg/mL; range, 11.2-92.2 pg/mL). Of these 33 neonates, 19 developed thrombocytopenia: nine of 19 (47%) had detectable IL-11 and 10 of 19 (53%) did not (p > 0.05). Although its role in platelet production in neonates remains unclear, these data suggest that IL-11 is involved in the endogenous cytokine response to sepsis or NEC in preterm neonates. Further studies of IL-11 in neonates are warranted to assess its role both in platelet production and in mediation of the endogenous inflammatory response.
 ...
PMID:Interleukin-11 levels in healthy and thrombocytopenic neonates. 1203 73

Thrombocytopenia remains a common problem in sick newborns. A quarter of all neonates admitted to neonatal intensive care units develop thrombocytopenia, and in 20% of episodes the thrombocytopenia is severe (platelets <50 x 10(9)/L). Practical and clinically relevant classifications of neonatal thrombocytopenia have now been developed which, by highlighting the principal conditions precipitating severe thrombocytopenia (eg, sepsis, necrotizing enterocolitis, perinatal asphyxia, and the immune thrombocytopenias), aid the practicing neonatologist. Recent reviews demonstrate that many neonates with severe thrombocytopenia receive repeated platelet transfusions, although evidence of their clinical benefit is lacking, and there exists a significant variation in platelet transfusion practice between centers. These facts support the need for the development of evidence-based protocols for platelet transfusion in the newborn and stimulate continued interest in the potential of hemopoietic growth factors (, thrombopoietin and interleukin-11) to prevent or treat neonatal thrombocytopenia.
 ...
PMID:Thrombocytopenia in the newborn. 1254 64

Thrombocytopenia is the most common hemostatic abnormality in sick newborn infants. Although many conditions may be associated with neonatal thrombocytopenia, low platelet counts in the first few days of life are often caused by fetomaternal problems, whereas thrombocytopenia developing after the third day is usually secondary to sepsis or necrotizing enterocolitis. Despite the frequency of thrombocytopenia in sick neonates, the underlying kinetic mechanisms are not always clear. The commonly accepted theories of decreased platelet production or increased consumption are being scrutinized in the light of new evidence. Thrombopoietin and interleukin-11 are being investigated to unravel the complex pathophysiology of thrombocytopenia in neonates and they are also being explored as potential therapeutic agents. Guidelines for platelet transfusions continue to be variable and controversial.
 ...
PMID:Thrombocytopenia in the newborn. 1496 90

Thrombopoietin (TPO) and its receptor (TPOR) are expressed in the central nervous system (CNS). Although TPO shares significant homology with various neurotrophins, recent data indicate a proapoptotic function of TPO in the CNS. In this study, TPO concentrations were analyzed in the cerebrospinal fluid (CSF) of neonates. Human neuroblastoma-derived SH-SY5Y cells were established to elucidate the effects of inflammation and hypoxia on neuronal Tpo expression. TPO was detectable in the CSF of 6 of 15 neonates with bacterial infection/sepsis (median 140, range 2-613 pg/mL), 5 of 9 neonates with posthemorrhagic hydrocephalus (median 31, range 1.4-469 pg/mL), 3 of 4 neonates with posthemorrhagic hydrocephalus plus bacterial infection/sepsis or meningitis (median 97, range 6-397 pg/mL), but not in controls ( n = 3). Neither the presence of detectable TPO nor its level in the CSF significantly correlated with any clinical or laboratory parameter. In SH-SY5Y cells, TPO and TPOR expression was detected by RT-PCR and Western blot analysis. In vitro, interleukin-6 (IL-6) did not significantly change Tpo gene expression. In contrast, Tpo mRNA expression significantly decreased under hypoxia, whereas erythropoietin (EPO) mRNA expression increased. In conclusion, our data provide evidence that in neuronal cells, TPO production is regulated by different mechanisms than in hepatocytes.
 ...
PMID:High thrombopoietin concentrations in the cerebrospinal fluid of neonates with sepsis and intraventricular hemorrhage may contribute to brain damage. 1731 41

We serially evaluated the effects of sepsis and/or necrotizing enterocolitis (NEC) on neonatal thrombopoiesis, using a panel of tests that included platelet counts, thrombopoietin concentrations (Tpo), circulating megakaryocyte progenitor concentrations (CMPs), and reticulated platelets (RPs). Variables analyzed included sepsis type, time after onset of sepsis, platelet counts, and gestational (GA) and postconceptional ages (PCA). Twenty neonates were enrolled. Ten had Gram-negative, six had Gram-positive, and four had presumed sepsis. Four neonates had NEC stage II or higher, and six developed thrombocytopenia. Overall, septic neonates had significantly elevated Tpo concentrations and circulating megakaryocyte progenitors. The highest Tpo levels were associated with Gram-negative or presumed sepsis. RP percentages were increased only in neonates with low platelet counts, while RP counts (RP% x platelet count) were elevated in neonates with high platelet counts. Our findings suggest that septic neonates up-regulate Tpo production, leading to increased megakaryocytopoiesis and platelet release, although the degree of upregulation is moderate. The changes in RP% and RP count most likely reflect increased thrombopoiesis with variable degrees of platelet consumption. In addition, our findings suggest that different factors, likely including level of illness and/or specific platelet or bacterial products, can down-regulate the magnitude of the thrombopoietic response.
 ...
PMID:Effects of sepsis on neonatal thrombopoiesis. 1855 13

Thrombopoietin (TPO) is a humoral growth factor that has been shown to increase platelet activation in response to several agonists. Patients with sepsis have increased circulating TPO levels, which may enhance platelet activation, potentially participating to the pathogenesis of multi-organ failure. Aim of this study was to investigate whether TPO affects myocardial contractility and participates to depress cardiac function during sepsis. We showed the expression of the TPO receptor c-Mpl on myocardial cells and tissue by RT-PCR, immunofluorescence and western blotting. We then evaluated the effect of TPO on the contractile function of rat papillary muscle and isolated heart. TPO did not change myocardial contractility in basal conditions, but, when followed by epinephrine (EPI) stimulation, it blunted the enhancement of contractile force induced by EPI both in papillary muscle and isolated heart. An inhibitor of TPO prevented TPO effect on cardiac inotropy. Treatment of papillary muscle with pharmacological inhibitors of phosphatidylinositol 3-kinase, NO synthase, and guanilyl cyclase abolished TPO effect, indicating NO as the final mediator. We finally studied the role of TPO in the negative inotropic effect exerted by human septic shock (HSS) serum and TPO cooperation with TNF-alpha and IL-1beta. Pre-treatment with the TPO inhibitor prevented the decrease in contractile force induced by HSS serum. Moreover, TPO significantly amplified the negative inotropic effect induced by TNF-alpha and IL-1beta in papillary muscle. In conclusion, TPO negatively modulates cardiac inotropy in vitro and contributes to the myocardial depressing activity of septic shock serum.
 ...
PMID:Thrombopoietin modulates cardiac contractility in vitro and contributes to myocardial depressing activity of septic shock serum. 2046 49


1 2 Next >>